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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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HMGB1 regulates autophagy through increasing transcriptional activities of JNK and ERK in human myeloid leukemia cells

  • Zhao, Mingyi (Department of Pediatrics, Xiangya Hospital, Central South University) ;
  • Yang, Minghua (Department of Pediatrics, Xiangya Hospital, Central South University) ;
  • Yang, Liangchun (Department of Pediatrics, Xiangya Hospital, Central South University) ;
  • Yu, Yan (Department of Pediatrics, Xiangya Hospital, Central South University) ;
  • Xie, Min (Department of Pediatrics, Xiangya Hospital, Central South University) ;
  • Zhu, Shan (Department of Pediatrics, Xiangya Hospital, Central South University) ;
  • Kang, Rui (Department of Pediatrics, Xiangya Hospital, Central South University) ;
  • Tang, Daolin (Hillman Cancer Center, University of Pittsburgh Cancer Institute) ;
  • Jiang, Zhigang (College of Life Sciences, Hunan Normal University) ;
  • Yuan, Wuzhou (College of Life Sciences, Hunan Normal University) ;
  • Wu, Xiushan (College of Life Sciences, Hunan Normal University) ;
  • Cao, Lizhi (Department of Pediatrics, Xiangya Hospital, Central South University)
  • Received : 2011.05.24
  • Accepted : 2011.07.18
  • Published : 2011.09.30
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Abstract

HMGB1 is associated with human cancers and is an activator of autophagy which mediates chemotherapy resistance. We here show that the mRNA levels of HMGB1 are high in leukemia cells and it is involved in the progression of childhood chronic myeloid leukemia (CML). HMGB1 decreases the sensitivity of human myeloid leukemia cells K562 to anti-cancer drug induced death through up-regulating the autophagy pathway, which is confirmed by the observation with an increase in fusion of autophagosomes and autophagolysosomes. When overexpressing HMGB1, both mRNA levels of Beclin-1, VSP34 and UVRAG which are key genes involved in mammalian autophagy and protein levels of p-Bcl-2 and LC3-II are increased. Luciferase assays document that over-expression of HMGB1 increases the transcriptional activity of JNK and ERK, which may be silenced by siRNA. The results suggest that HMGB1 regulates JNK and ERK required for autophagy, which provides a potential drug target for therapeutic interventions in childhood CML.

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References

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